Inflammation is increasingly recognized to play a central role in atherosclerosis and coronary artery disease, and peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these potentially modifiable risk markers to prognosis after ischemic stroke is less clear. The proposed study, Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS), is an approved ancillary study to the on-going NINDS-funded Secondary Prevention of <Small Subcortical Strokes, or SPSS trial (NINDS UO1 NS038529 04A1, Principal Investigator O Benavente), a large, Phase 3, multicenter, 2X2 factorial, randomized clinical trial of anti-platelet therapy and anti-hypertensive therapy in patients with lacunar stroke. This ancillary study will test the following hypotheses: (1) high sensitivity C-reactive protein, serum amyloid A, and CD40 ligand levels are independent risk factors for (a) recurrent ischemic stroke and (b) other vascular outcomes including death; (2) the efficacy of dual antiplatelet treatment with clopidogrel and aspirin versus aspirin alone in reducing risk of recurrent stroke is greater among those patients with elevated levels of these markers; (3) inflammatory marker levels are independent risk factors for cognitive decline in patients with lacunar infarcts; (4) treatment with clopidogrel plus aspirin will reduce levels of these markers more than aspirin alone in patients with lacunar stroke. Levels of these markers will be measured using nephelometric and immunoassay techniques on serum samples collected at enrollment and at one year from 1440 SPSS subjects. Information on concomitant infectious, neoplastic, and inflammatory diseases that might contribute to inflammation will also be collected. Outcomes of recurrent ischemic stroke, myocardial infarction, vascular mortality and total mortality will be ascertained. Cox proportional hazard model analysis will be used to assess the significance of the main exposure variables after adjustment for other risk factors, statin treatment, center, and SPSS treatment group. Analysis will also be performed stratified by dual versus single antiplatelet therapy. The present study will maximize efficiency in addressing these questions by utilizing the existing protocol and organizational structure of SPSS for recruitment, interaction with sites, follow-up, and event ascertainment.